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April 19, 2012

Possible Antidote For Cocaine Overdose Emerges

by editor

Connie K. Ho for RedOrbit.com

Found in more than 400,000 emergency room visits and related to 5,000 overdose deaths a year in the United States, cocaine is a highly dangerous drug that can lead to death. Scientists at the Scripps Institute of Research decided to tackle this issue head on with a study that examines a solution that can be injected to reverse the effects of cocaine overdose in emergency situations. With the solution´s success in trials with mice, the researchers hope to complete more tests to show the possible therapeutic potential of a human antibody against cocaine.

The report, published in the American Chemical Society´s journal Molecular Pharmaceutics, is a collaboration between Kim Janda, a professor in the Department of Immunology and Microbial Science as well as director of the Worm Institute for Research and Medicine, and Jennifer B. Treweek, PhD, a research associate in Janda's laboratory. The team has worked on developing vaccines against cocaine, heroin, nicotine, and even the "date-rape" drug Rohypnol. Many of the vaccines have been “active” vaccines, which are useful against addiction and relapse but not in overdose emergencies.

With cocaine overdoses, possible consequences include hyperthermia, irregular heartbeats, seizures, and death. To address these issues, a possibility for the cocaine antidote would be an “active” vaccine that would be a ready-made solution of antibodies, similar to vaccines used to treat snakebites. The “active” vaccine would find antibodies that could bind to circulating cocaine molecules and prevent the drug from reaching the brain.

In 2005, a study by Janda and other colleagues found that injections of a mouse-derived anti-cocaine antibody, GNC92H2, could keep mice alive despite cocaine in the body. The study completed by Janda and Treweek used a genetically engineered mouse to create fully human antibodies against cocaine molecules, known as GNCgzk. These antibodies could bind ten-times more effectively than GNC92H2. Furthermore, the report by Janda and Treweek discussed developing a “passive” vaccine that would be made up of pre-formed human antibodies against cocaine that would be 10 times more powerful in binding cocaine molecules. This vaccine could be used to reverse cocaine toxicity and become a life-saving therapy for overdose victims.

"This would be the first specific antidote for cocaine toxicity," said Janda, PhD, senior author of the report and a leader in the field of vaccines against drugs of abuse. "It's a human antibody so it should be relatively safe, it has a superior affinity for cocaine, and we examined it in a cocaine overdose model that mirrors a real-life scenario.”

With the success of the second study, Janda and Treweek are looking into economically-friendly ways to produce F(ab')2-gzk, a simpler version of GNCgz, in large amounts. The new treatment could help reduce the immediate effects of overdose and prevent patients´ drug relapse. They hope that the drug could later be utilized in recovery or detox programs, given to supplement other medications, and generally aid drug addicts the recovery period.

"A lot of people that overdose end up going back to the drug rather quickly," explained Janda in a statement. “But this antibody would stay in their circulation for a few weeks at least, and during that time the drug wouldn't have an effect on them."